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United States Patent | 6,139,817 |
Palmer ,   et al. | October 31, 2000 |
The present invention provides a method for determining pathogen sensitivity to varying levels of reduction of a gene product using an expression vector system having a promoter that is essentially off in vitro and turns on selectively during the infection process in vivo. Genes and gene products identified by this method as essential to growth of infection of a selected pathogen are also provided. In addition, therapeutic compositions designed to target genes identified by this method are provided.
Inventors: | Palmer; Leslie M. (Malvern, PA); Pratt; Julie M. (Verona, IT); Rosenberg; Martin M. (Royersford, PA) |
Assignee: | Smithkline Beecham Corporation (Philadelphia, PA) |
Appl. No.: | 010523 |
Filed: | January 21, 1998 |
Current U.S. Class: | 424/9.1; 424/9.2; 424/93.2; 424/93.6; 435/6; 435/7.1; 435/7.2; 435/29; 435/252.3; 435/252.31; 435/252.33; 435/252.34; 435/252.35; 435/320.1; 536/23.1; 536/24.1 |
Intern'l Class: | A61K 049/00; C12N 015/63; C12Q 001/68 |
Field of Search: | 435/6,7.1,7.2,29,320.1,252.3,252.31,252.33,252.34,252.35 424/9,93.2,93.6 |
5756305 | May., 1998 | Timberlake et al. | 435/34. |
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Agius et al., Advances in Virus Research, vol. 44, pp. 357-379, 1994. Harold M. Weintrob, "Antisense RNA and DNA", Scientific American, pp. 40-46 (Jan. 1990). Hensel, et al., "Simultaneous Identification of Bacterial Virulence Genes By Negative Selection", Science, vol. 269, pp. 400-403, (1995). Guerrier-Takada, et al, "Artificial Regulation of Gene Expression in Escherichia coli by Rnase P", Proc. Natl Acad. Sci. USA, vol. 92:, pp 11115-11119, (Nov. 1995). Lee, et al., J. Infect. Dis. vol. 156; 741, (1987). Fields, et al., Proc. Natl. Acad. Sci., vol. 83: 5189, (1986). Finlay, et al., Mol. Microbiol., vol. 2: 757, (1988). Miller, et al., Infect. Immun., vol. 57: 2758, (1989). Bolker, et al., Mol. Gen. Genet., vol. 248: 547-552, (1994). Augustin, et al., Eur. J. Biochem., vol. 204: 1149-1154, (1992). Slauch, et al., Methods in Enzymology, vol. 235: 481-492, (1994). |
5'-GATGCAGAAGCGATTTACACGTACGAAGGT [SEQ ID NO:1] ACACATGAAATTAATGCCTTAGTAATTGGACGCGCTTTGACTGGAGATTCTGCTTTCGTATAAATAGC AAATAATTATATGAGATGCATTAATTTCACTAAAAAAGACTTATTTTAAGCATAAAGCTTTTTCCTTA AATAAGAGGCTAAGATGACTGTCAAAGATACTTAATTAATTTTATAAAATAGCAACGTTATTCCAATT ATCTTAATGGTTATCTTATCCTCAACTAAATTGGAGGAATCACTATG . . .3'
__________________________________________________________________________ # SEQUENCE LISTING - <160> NUMBER OF SEQ ID NOS: 1 - <210> SEQ ID NO 1 <211> LENGTH: 281 <212> TYPE: DNA <213> ORGANISM: Staphylococcus aureus - <400> SEQUENCE: 1 - gatgcagaag cgatttacac gtacgaaggt acacatgaaa ttaatgcctt ag - #taattgga 60 - cgcgctttga ctggagattc tgctttcgta taaatagcaa ataattatat ga - #gatgcatt 120 - aatttcacta aaaaagactt attttaagca taaagctttt tccttaaata ag - #aggctaag 180 - atgactgtca aagatactta attaatttta taaaatagca acgttattcc aa - #ttatctta 240 # 281 caac taaattggag gaatcactat g __________________________________________________________________________